The principal aim of this study was to investigate the effects of ketanserin on peripheral vascular pressor mechanisms in nine patients with essential hypertension, including an assessment of the responsiveness to intravenous infusions of the alpha 1-adrenergic agonist, phenylephrine, and the nonadrenergic vasoconstrictor, angiotensin II. There were small but significant rightward shifts in the phenylephrine pressor dose-response curves (by 1.5- to twofold) following ketanserin but no shifts for angiotensin II. This modest shift in phenylephrine responsiveness contrasted with the fivefold shift obtained with a single oral dose (1 mg) of prazosin. The relationship between the phenylephrine-induced increase in blood pressure and the reduction in heart rate was used as an index of baroreflex responsiveness: there were no significant effects attributable to ketanserin. There were no significant differences in plasma aldosterone or renin activity, nor in 24-h urinary volume or electrolytes, following ketanserin. The principal mechanism underlying the antihypertensive effect of ketanserin is unlikely to involve peripheral vascular alpha 1-adrenoceptor antagonism, altered baroreflex responsiveness, or perturbation of the renin-angiotensin-aldosterone system.